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Biomedical subjects

N J George

Publications and source records attributed to N J George.

At least 19 recordsLinked to original sources
PubMed1992

Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer.

In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour-free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton.

Alkaline Phosphatase↗
PubMed1992

Levels of prostate specific antigen that predict skeletal spread in prostate cancer.

The ability of serum prostate specific antigen (PSA) and serum acid phosphatase (SAP) to identify skeletal spread was evaluated in untreated patients with prostatic cancer. Twenty patients with scintigraphic evidence of metastatic disease in bone (M1) at diagnosis were compared with 50 untreated patients in whom scans were repeatedly negative during long-term surveillance. Using the present laboratory upper limit of normal (ULN) of 3 iu/l, the sensitivity and specificity of SAP for M1 disease were 80 and 86% respectively. Stepwise discriminant analysis demonstrated that SAP was able to stage patients correctly (bone scan positive or negative) with 81% predictive accuracy at an optimum cut-off limit of 4.6 iu/l. By contrast, whilst PSA (Hybritech) was 100% sensitive for skeletal disease at 10 ng/ml--at the expense of poor (36%) specificity--analysis determined that an optimum cut-off limit of 58 ng/ml led to 79% predictive accuracy for disease in bone. It was concluded that PSA levels > 58 ng/ml are highly indicative of spread to the skeleton, even in the absence of radiological or scintigraphic evidence of metastases.

Acid Phosphatase↗
PubMed1992

Outcome and prognostic factors in patients with advanced prostate cancer and obstructive uropathy.

In a series of 51 patients with prostate cancer and obstructive uropathy, unilateral or bilateral obstruction was identified in 22 (43%) and 29 (57%) respectively. This included a non-functioning kidney in 12 patients. In 86% of patients the T category was advanced. Bone metastases were present in 36 cases (71%); 19 patients (37%) had chronic retention. All patients with metastatic disease underwent hormonal manipulation and 43 underwent transurethral resection of the prostate. External beam radiotherapy, percutaneous nephrostomy and ureteric reimplantation were performed in 4, 5 and 1 patient respectively. Actuarial survival of all 51 patients was 57 and 25% at 2 and 5 years. Presentation with bilateral or non-function did not predict a worse prognosis in comparison with patients with unilateral hydroureteronephrosis. Raised alkaline phosphatase and prostatic acid phosphatase were of no prognostic value, while creatinine reached marginal significance. A positive bone scan and raised urea were strongly predictive of a poor outlook. It was concluded that prostate cancer and obstructive uropathy should not uniformly imply a terminal event, and interventional therapy is justified with a 25% 5-year survival rate.

Actuarial Analysis↗
PubMed1991

Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study.

Twenty five hormone manipulated patients with prostate cancer and metastatic bone disease, treated at least 6/12 previously by hormone manipulation, were given intravenous infusions of Disodium Pamidronate (APD) over a 6 month period. Patients received 30 mg weekly for 4 weeks then twice monthly for 5 months. No other treatment was administered during study. Eleven of 17 patients with pain at the start of the study were pain free at the end. Fasting morning calcium excretion and serum osteocalcin fell significantly with Pamidronate (P less than 0.0001) and urine hydroxyproline was lowered in 13/20 evaluable patients at 6 months. Alkaline phosphatase fell in a proportion of patients and five of 17 patients with previously progressive bone scans stabilised (4) or regressed (1) on treatment. Rising acid phosphatase levels were also lowered in five patients. It is concluded that Pamidronate may be effective in palliating bone pain in some patients and has a stabilising influence on abnormally high bone turnover in metastatic prostate cancer. Further controlled studies of the compound are now warranted.

Aged↗
PubMed1991

Relationship between bladder morphology and long-term outcome of treatment in patients with high pressure chronic retention of urine.

A group of 32 men undergoing bladder outflow surgery for high pressure chronic retention (HPCR) of urine were studied prospectively. At the time of treatment marked morphological changes in the bladder wall were demonstrated histologically, but after a mean follow-up of 42.9 months residual urine had decreased significantly and renal function had improved or stabilised in 28 patients (84%). Four patients deteriorated but in 3 of these another potential cause for loss of renal function was present. The majority of patients have a good long-term prognosis following treatment for HPCR.

Adult↗
PubMed1991

Morphometric evidence for bone resorption and replacement in prostate cancer.

A series of 78 patients with metastatic bone disease from prostate cancer underwent iliac crest biopsy, enabling histomorphometric quantification of eroded bone surface and bone volume in both tumour-free and metastatic bone tissue. Eroded surfaces in tumour-free specimens were high in patients with active compared to stable disease but bone volume was maintained in both groups, whilst in bone surrounding micrometastases (n = 8) eroded surfaces were further increased and bone volume reduced. Eroded surfaces within metastases were greater still but were associated with increased bone volume due to replacement of the existing trabecular tissue with abnormal woven bone, giving an overall appearance of sclerosis. These results show that the effect of prostate cancer on bone tissue is complex, involving differential disturbance of bone formation and resorption within metastases, in bone surrounding tumour invasion and in the tumour-free skeleton.

Bone Neoplasms↗
PubMed1991

Disturbance in sodium regulating hormones in chronic obstructive uropathy.

Serum atrial natriuretic peptide (ANP), plasma renin activity (PRA), angiotensin II (AII) and aldosterone levels have been studied in patients with chronic bilateral ureteric obstruction resulting from high pressure chronic retention of urine (HPCR), both in the obstructed state and during the post-obstructed period. Increased ANP levels observed during chronic obstruction fell rapidly following urinary tract decompression by urethral catheterisation. Serum ANP resurged briefly within 24 h but stabilised thereafter at a lower level. PRA was initially suppressed but rose after catheterisation, the increase lagging behind the changes seen for ANP. Rising levels of AII and aldosterone followed this trend but, unlike PRA, levels were not completely suppressed in the obstructed state. The observed hormonal changes probably reflect homeostatic mechanisms directed to the maintenance of sodium and water balance during obstruction and to limitation of the diuresis following its relief.

Aged↗
PubMed1991

Preferential preservation of bone mineralisation by LHRH agonists in the treatment of metastatic prostate cancer.

Histomorphometric measurements of tumour-free bone have been undertaken in a closely matched group of patients with metastatic prostate cancer treated either by subcapsular orchidectomy (SCO) or luteinising hormone-releasing hormone (LHRH) agonists. Age, fasting morning urine hydroxyproline/creatinine ratios, alkaline and acid phosphatase levels and elapsed time after hormonal manipulation were similar in those receiving SCO (n = 8) as compared to LHRH therapy (n = 8). Results indicated that osteoid surface and mineralisation rate were significantly reduced in the SCO group (p less than 0.05); other indices were also lower in the SCO patients but failed to reach statistical significance. These changes, possibly due to increased adrenal cortical stimulation secondary to elevated gonadotrophin levels following orchidectomy suggest that medical castration by gonadotrophin inhibition may avoid unnecessary morbidity due to treatment-induced bone dysfunction.

Aged↗
PubMed1990

Effect of bladder filling on upper tract urodynamics in man.

A group of 21 patients with hydronephrosis but normal bladders had their upper urinary tract pressures monitored while perfusing the affected kidneys through a fine bore nephrostomy tube, initially with the bladder on free drainage and subsequently during bladder filling. In 7 patients the renal pelvic pressures were altered by bladder filling and loin pain was reproduced in 4. It was concluded that with high upper tract flow rates, vesical filling can affect upper tract dynamics and this should be considered when evaluating patients with loin pain or potential obstructive uropathy.

Female↗
PubMed1990

Increased survival of patients with massive lymphadenopathy and prostate cancer: evidence of heterogeneous tumour behaviour.

The survival of patients with prostate cancer and radiologically detectable lymph node enlargement has been studied prospectively over an 8-year period. Computed tomography in 108 patients presenting with symptoms, signs or biochemical results suggesting lymphatic spread revealed pelvic or abdominal node masses in 60 patients; in 29 (48%), the masses measured more than 4 cm and the maximum node diameter was 15 cm. Two-thirds of patients had advanced (T3/T4) tumour stage. Following treatment, actuarial survival in all 60 patients with nodal enlargement was 40% at 5 years. Within this group, survival in 22 patients with lymphadenopathy but negative bone scans at diagnosis was significantly better than that of 38 patients with both node and bone disease (70% vs 20% at 5 years). This improvement was related both to an apparent inability of certain tumours initially to progress and seed within bone and to a marked sensitivity of the node masses to subsequent hormonal manipulation. Primary tumour grade was proportionally similar in both groups. Unexpectedly, 6 of the 38 patients with combined disease obtained a complete remission after treatment. The reason for this heterogeneous biological behaviour remains unclear; but these observations underscore the importance of vigorous treatment in all patients with advanced lymph node disease.

Aged↗
PubMed1989

Assessment of the nephron segments involved in post-obstructive diuresis in man, using lithium clearance.

The phenomena of post-obstructive diuresis and natriuresis have been studied using the lithium clearance technique in 10 patients with high pressure chronic retention. Following relief of obstruction there was a significant increase in both sodium and water excretion. There was a coincident reduction in the fractions of sodium and water reabsorbed in both proximal and distal nephron segments. This study demonstrates for the first time that following relief of chronic obstructive uropathy in man, changes in sodium and water excretion are due to altered handling in both proximal and distal nephron segments.

Aged↗
PubMed1988

Natural history of localised prostatic cancer managed by conservative therapy alone.

The natural history of localised prostatic cancer was studied prospectively over 7 years. Within a single health district all patients with histologically confirmed cancer and negative 99mTc bone scans were managed, irrespective of clinical stage or pathological grade, according to a conservative regimen that included no form of anti-cancer treatment other than endoscopic resection for relief of urinary symptoms. Complete records were compiled on 120 of 152 patients (mean age 74.8 years, range 62-90) without metastases at diagnosis. Local tumour increased to palpable dimensions (T2/T3) in 100 of these patients (84%) but metastases developed in only 13, the mean time to scan conversion being 35.8 months. 23 patients were withdrawn from study and treated because of concern about increasing tumour size, and metastases developed in 1 of these. 5 patients died of prostatic cancer but the disease was not responsible for 48 additional deaths. Actuarial survival rates (excluding non-cancer deaths) at 5 and 7 years were 80% and 75%, respectively; the corresponding rate for those with metastases at presentation was 13% at 5 years. The likelihood that prostatic cancer will cause death within 7 years is indicated primarily by the scintigraphic findings at diagnosis.

Aged↗
PubMed1988

Mechanism of upper tract dilatation in patients with thick walled bladders, chronic retention of urine and associated hydroureteronephrosis.

The mechanism of upper tract dilatation in patients with obstructive uropathy associated with thick walled trabeculated bladders and painless retention of urine has been determined in 9 cases by simultaneous measurement of renal pelvic and bladder pressures under baseline conditions and after administration of different stresses to the urinary tract. Under basal conditions no pelvic pressure increase was observed during detrusor contraction or other alteration of lower urinary tract pressure. However, after the flow in the upper tract was increased by oral water load, intravenous furosemide or direct pelvic perfusion, pelvic pressures were markedly elevated and reflected accurately any change in intravesical pressure. Under such conditions, pelvic pressures frequently exceeded 40 cm. water. These observations provide an explanation for the increasing size of the upper tract and a clarification of the mechanism whereby renal function might gradually deteriorate in these patients.

Aged↗
PubMed1988

The biphasic nature of renal functional recovery following relief of chronic obstructive uropathy.

Twenty-one patients with chronic obstructive uropathy due to high pressure chronic retention of urine underwent renal functional assessment both during the period of obstruction and repeatedly up to 3 months following its relief. Glomerular filtration rate (GFR) was determined using clearance of 99mTc-DTPA and iohexol. Creatinine, water, urea and electrolyte excretion was assessed from timed urine collections. Excretion of water, urea and electrolyte was normal during obstruction but increased dramatically immediately following relief (e.g. sodium 110 to 234 mmol/24 h). Values returned to normal by 2 weeks (sodium excretion 148 mmol/24 h). No further significant changes occurred up to 3 months. Mean 99mTc-DTPA and iohexol clearances during obstruction were 59.0 and 50.5 ml/min respectively. Following relief of obstruction, no significant improvement occurred at 2 weeks but did at 3 months (mean = 68.4 and 55.7 ml/min). Mean creatinine clearance during obstruction was 32.5 ml/min. This improved 2 days following relief to 46 ml/min. No further improvement was seen until 3 months (mean = 57.3 ml/min). It was concluded that recovery of renal function from obstructive injury occurs in two phases, an early tubular phase lasting up to 2 weeks and a later, predominantly glomerular phase, between 2 weeks and 3 months. There is some disparity between creatinine clearance and more accurate measurements of GFR which may be explained by tubular excretion of creatinine in the early phase of recovery.

Adult↗
PubMed1987

Reversible hypertension associated with unrecognised high pressure chronic retention of urine.

The cardiovascular effects of relief of obstruction were examined in 21 patients with painless urinary retention and hydronephrosis and hydroureter associated with hypertension (diastolic blood pressure 95-120 mm Hg, mean 107, 11 patients), severe peripheral oedema (8 patients), raised jugular venous pressure (5 patients), or clinical evidence of pulmonary oedema (5 patients). Before relief of obstruction fractional sodium excretion was appropriate for the reduced rate of glomerular filtration. After urethral catheterisation blood pressure fell (p less than 0.001) and the other cardiovascular abnormalities were rapidly reversed without further therapeutic measures. This improvement was associated with an increase (p less than 0.05) in both absolute and fractional urinary sodium excretion that was greatest at 24 h. 5% of patients undergoing surgery for obstructive disorders of the lower urinary tract have hydronephrosis and hydroureter. Hypertension related to chronic urinary tract obstruction may be the commonest form of surgically correctable renal hypertension.

Adult↗